This invention relates to measuring cell physical properties and more particularly to using a suspended microchannel resonator to determine cell buoyant mass and deformability.
It is known that the transit time of a cell through a pore depends on the physical properties of the cell. Theoretical analyses have also shown that transit time depends on the cell's size and deformability. Transit times are altered in sepsis, a process in which inflammatory mediators in the bloodstream activate neutrophils, and in leukostasis, an often fatal and poorly understood complication of acute leukemia.
A cell's mechanical property such as deformability can also provide a window on how disease states influence a single cell's biomechanics. For example, studies have examined the effect of a malaria-producing parasite on deformability of human red blood cells. See, “Biomechanics and biophysics of cancer cells” by Subra Suresh, Acta Biomaterialia 3 (2007) 413-438. It is also known that the deformability of cancer cells has implications for cell signaling, cytoadherence, migration, invasion and metastatic potential. Therefore, knowledge of a cell's deformability is important for selecting appropriate diagnostic and treatment protocols.
Cell mechanical properties have been determined using atomic force microscopes, laser/optical tweezers, mechanical microplate stretchers, micro-postarray deformation with patterned microarrays that serve as cell substrates and micropipette aspiration. These techniques are limited by relatively low throughput.
Microfluidic and nanofluidic assays using rigid or compliant channels have also been used to simulate the flow of cells through blood vessels, and in conjunction with quantitative cell deformability assays, such as optical tweezers, to study the elastic and viscoelastic characteristics of cells. See, Rosenbluth et al., “Analyzing cell mechanics in hematologic diseases with microfluidic biophysical flow cytometry,” Lab Chip, Volume 81, No. 7, July 2008, pp 993-1228; and Hirose, et al., “A New Stiffness Evaluation toward High Speed Cell Sorter,” 2010 IEEE International Conference on Robotics and Automation, May, 2010. See also, Hou et al., “Deformability study of breast cancer cells using microfluidics,” Biomed Microdevices, Volume 11, No. 3, June 2009, pp 557-564. The contents of all of the references cited herein are incorporated by reference in this application in their entirety.
It is therefore an object of the present invention to provide a high-throughput system for determining a cell's buoyant mass and deformability that enables the dependencies of transit time through a constriction on deformability and size to be decoupled using a suspended microchannel resonator.